2000D-1392 Guidance for Industry on Botanical Drug Products
FDA Comment Number : EC8
Submitter : Mr. Avi Harris Date & Time: 03/25/2005 04:03:14
Organization : Mazal Plant Pharmaceuticals
Category : Drug Industry
Issue Areas/Comments
GENERAL
GENERAL
The FDA distinguishes between two types of botanical drug products: those that are legally marketed and those that are either not lawfully marketed anywhere or have known safety issues.
We have a general comment regarding clarification of the term "legally marketed (under the DSHEA)" and a specific comment regarding the required additional CMC information recommended for Raw Materials comprising botanical drug products not lawfully marketed anywhere.

1) Section VI, subsection A, 4th para. states: "In contrast to botanical products that have been marketed in some form, considerably less information may be available on the safety of a new botanical product that has not been marketed anywhere as a food or dietary supplement and has not been tested as a drug in humans." This sems to imply, and in our opinion correctly so, that a botanical product that is based upon a legally marketed supplement under the DSHEA, but which has minor addition or deletion from the marketed dietary supplement *multiplant* formulation, would fall under the category of a legally marketed botanical poduct. This should be clarified in this section, probably in the first para. of this section (A), as follows: Instead of "As noted above....as long as....and it is to be used at approximately the same doses as those currently or traditionally used or recommended." we suggest the following: "As noted above....as long as....and it consists of approximately the same formulation and is to be used at approximately the same doses as those currently or traditionally used or recommended."

2) In section VIII, subsections A. and B. 1.: No distinction is made in the data necessary for each individual raw material between those that are legally marketed and those that are not. We recommend that the expanded recommendation of the FDA for suplemental data (in sections A. and B. 1.) for a botanical drug product not legally marketed, relate specifically to those raw materials that are not legally marketed, GRAS, etc... A recommended revision of these sections is herewith suggested:
Section VIII A., instead of "In addition to the information outlined in section VII.A.1-2, the following should be provided in accordance with the listed subsections of ? 312.23 for each raw material contained in a botanical product not lawfully marketed in either the United States or other countries:"
We suggest:
"In addition to the information outlined in section VII.A.1-2, the following should be provided in accordance with the listed subsections of ? 312.23 for each not lawfully marketed raw material contained in a botanical product not lawfully marketed in either the United States or other countries:"
in section VIII B. 1.: instead of "A botanical drug substance can be derived from one or more botanical raw materials. The following recommendations apply to each individual botanical raw material used."
we suggest:
"A botanical drug substance can be derived from one or more botanical raw materials. The following recommendations apply to each individual botanical raw material used that is not legally marketed."

Thank you for the opportunity to present these suggestion to you.

Sincerely,

Avi Harris
Director of Regulatory and Clinical Operations
Mazal Plant Pharmaceuticals.